Bottom Line:
The recurrent and familial forms of ANE were found to be incompletely autosomal-dominant.The treatment of ANE is still under investigation.We summarize the up-to-date knowledge on ANE, with emphasis on prompt diagnosis and better treatment of this rare but fatal disease.

ABSTRACTAcute necrotizing encephalopathy (ANE) is a rare but distinctive type of acute encephalopathy with global distribution. Occurrence of ANE is usually preceded by a virus-associated febrile illness and ensued by rapid deterioration. However, the causal relationship between viral infections and ANE and the exact pathogenesis of ANE remain unclear; both environmental and host factors might be involved. Most cases of ANE are sporadic and nonrecurrent, namely, isolated or sporadic ANE; however, few cases are recurrent and with familial episodes. The recurrent and familial forms of ANE were found to be incompletely autosomal-dominant. Further the missense mutations in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2) were identified. Although the clinical course and the prognosis of ANE are diverse, the hallmark of neuroradiologic manifestation of ANE is multifocal symmetric brain lesions which are demonstrated by computed tomography (CT) or magnetic resonance imaging (MRI). The treatment of ANE is still under investigation. We summarize the up-to-date knowledge on ANE, with emphasis on prompt diagnosis and better treatment of this rare but fatal disease.

fig3: Diffusion MRI and susceptibility weighted imaging (SWI) findings of acute necrotizing encephalopathy (ANE). (a) was the schematic diagram of typical tricolor pattern corresponding to the thalamic lesions on (b) (a: center of thalamic lesions characterized by hemorrhage and necrosis; b: periphery of the central thalamic lesions characterized by cytotoxic edema; c: outside portions of the thalamic lesions suggesting vasogenic edema). (b) and (c), (d) and (e) were the apparent diffusion coefficient (ADC) and diffusion-weighted image (DWI), respectively, at onset which suggested the bilateral thalamus and brain stem lesions (blue arrow). (f) and (g), (h) and (i) were the ADC and DWI imaging of follow-up which revealed disappearance of the brain stem lesions and hemosiderin deposition on bilateral thalamus (red arrow). (j), (k), and (l) were the follow-up SWI images which showed hemosiderin deposition in the bilateral thalami and the cerebella (red arrow).

Mentions:
Neuroradiologic manifestations are characterized by dynamic changes during the clinical course corresponding to pathophysiological changes from edema to petechial hemorrhage and then to necrosis [1, 2]. Regression or recovery of the brain lesions is possible for survivors [1–4]. Herein we explain the dynamic imaging changes in the brain of ANE by exhibiting the neuroimages of our patient with ANE (Figures 2 and 3). Lesions in the brain are edematous and combined with mass effect at the onset of ANE. Hypodensities are frequently seen on CT (Figure 2(a)) and homogeneously prolonged T1 (Figures 2(b) and 2(c)) and T2 (Figures 2(d) and 2(e)) relaxation time (Figures 2(b) and 2(c)) of the brain lesions on MRI are found in most patients. Moreover, the feature of restricted water diffusibility on diffusion MR including diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) (Figures 3(b), 3(c), 3(d), and 3(e)) can be found in a majority of ANE patients [10, 11, 18–20, 22–26, 35–37, 45, 67]. Gradually, with the resolution of edema and mass effect, the feature of petechial hemorrhage and necrosis appears, and hypodense areas on CT become mottled because of the irregular hyperdense spots at the center which result from the extravasation of blood vessels or petechial hemorrhage [35, 59]. On the corresponding T1-weighted imaging (T1WI), increased signal intensities in the center surrounded by the decreased signals are detected, while T2-weighted imaging (T2WI) may reveal decreased signal intensities that are surrounded by increased or homogeneous increased signal intensities [5, 10, 26, 67]. Small petechial hemorrhage is usually obscure. The T2*-weighted gradient echo imaging or the susceptibility weighted imaging (SWI) is more sensitive in showing the petechial hemorrhage of ANE, both of which demonstrate low signal intensities [9, 67, 68].

fig3: Diffusion MRI and susceptibility weighted imaging (SWI) findings of acute necrotizing encephalopathy (ANE). (a) was the schematic diagram of typical tricolor pattern corresponding to the thalamic lesions on (b) (a: center of thalamic lesions characterized by hemorrhage and necrosis; b: periphery of the central thalamic lesions characterized by cytotoxic edema; c: outside portions of the thalamic lesions suggesting vasogenic edema). (b) and (c), (d) and (e) were the apparent diffusion coefficient (ADC) and diffusion-weighted image (DWI), respectively, at onset which suggested the bilateral thalamus and brain stem lesions (blue arrow). (f) and (g), (h) and (i) were the ADC and DWI imaging of follow-up which revealed disappearance of the brain stem lesions and hemosiderin deposition on bilateral thalamus (red arrow). (j), (k), and (l) were the follow-up SWI images which showed hemosiderin deposition in the bilateral thalami and the cerebella (red arrow).

Mentions:
Neuroradiologic manifestations are characterized by dynamic changes during the clinical course corresponding to pathophysiological changes from edema to petechial hemorrhage and then to necrosis [1, 2]. Regression or recovery of the brain lesions is possible for survivors [1–4]. Herein we explain the dynamic imaging changes in the brain of ANE by exhibiting the neuroimages of our patient with ANE (Figures 2 and 3). Lesions in the brain are edematous and combined with mass effect at the onset of ANE. Hypodensities are frequently seen on CT (Figure 2(a)) and homogeneously prolonged T1 (Figures 2(b) and 2(c)) and T2 (Figures 2(d) and 2(e)) relaxation time (Figures 2(b) and 2(c)) of the brain lesions on MRI are found in most patients. Moreover, the feature of restricted water diffusibility on diffusion MR including diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) (Figures 3(b), 3(c), 3(d), and 3(e)) can be found in a majority of ANE patients [10, 11, 18–20, 22–26, 35–37, 45, 67]. Gradually, with the resolution of edema and mass effect, the feature of petechial hemorrhage and necrosis appears, and hypodense areas on CT become mottled because of the irregular hyperdense spots at the center which result from the extravasation of blood vessels or petechial hemorrhage [35, 59]. On the corresponding T1-weighted imaging (T1WI), increased signal intensities in the center surrounded by the decreased signals are detected, while T2-weighted imaging (T2WI) may reveal decreased signal intensities that are surrounded by increased or homogeneous increased signal intensities [5, 10, 26, 67]. Small petechial hemorrhage is usually obscure. The T2*-weighted gradient echo imaging or the susceptibility weighted imaging (SWI) is more sensitive in showing the petechial hemorrhage of ANE, both of which demonstrate low signal intensities [9, 67, 68].

Bottom Line:
The recurrent and familial forms of ANE were found to be incompletely autosomal-dominant.The treatment of ANE is still under investigation.We summarize the up-to-date knowledge on ANE, with emphasis on prompt diagnosis and better treatment of this rare but fatal disease.

ABSTRACTAcute necrotizing encephalopathy (ANE) is a rare but distinctive type of acute encephalopathy with global distribution. Occurrence of ANE is usually preceded by a virus-associated febrile illness and ensued by rapid deterioration. However, the causal relationship between viral infections and ANE and the exact pathogenesis of ANE remain unclear; both environmental and host factors might be involved. Most cases of ANE are sporadic and nonrecurrent, namely, isolated or sporadic ANE; however, few cases are recurrent and with familial episodes. The recurrent and familial forms of ANE were found to be incompletely autosomal-dominant. Further the missense mutations in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2) were identified. Although the clinical course and the prognosis of ANE are diverse, the hallmark of neuroradiologic manifestation of ANE is multifocal symmetric brain lesions which are demonstrated by computed tomography (CT) or magnetic resonance imaging (MRI). The treatment of ANE is still under investigation. We summarize the up-to-date knowledge on ANE, with emphasis on prompt diagnosis and better treatment of this rare but fatal disease.